Recent advances in the treatment and monitoring of HIV-1 infection have substantially diminished HIV-associated illness and mortality;however the management of HIV-infected patients has become increasingly complex. We are conducting studies that: (1) define the hepatitis C viral response to pegylated interferon-based therapy in HIV co-infected individuals, (2) evaluate novel therapeutic strategies in the management of hepatitis C virus (HCV) in HIV-co-infected individuals, and (3) develop novel genomic and proteomic markers that predict HCV response to existing and novel therapies. Analyses of the kinetics of the viral response to standard HCV therapy in HCV/HIV co-infected individuals suggest that it may be possible to predict a long term response to anti-HCV therapy based on the initial response to therapy of HCV levels in plasma. Using combination therapy of pegylated interferon together with ribavirin in these subjects, we are determining whether genomic and proteomic markers can predict response to therapy prior to initiation of treatment. Subsequent clinical trials will determine whether more frequent doses of pegylated interferon or novel albumin-conjugated interferon alpha (Alb-interferon) in combination with ribavirin enhance the viral kinetic response to HCV therapy in persons co-infected with HCV and HIV.